For virulence factor identification we use tools of functional genomics. Usually, the first step comparative proteomics and/or bioinformatics reveal potential factors of virulence that must be verified employing method of gene disruption (allelic replacement or insert mutagenesis). Afterwards, prepared mutants with defective gene undergo in vivo and in vitro testing. Interaction of the pathogen with macrophages is performed using so called method of cell surface capturing or studies of membrane rafts after pathogen stimuli with subsequent quantitative proteomic analysis. Another that is being established at our institute is fluorescence microscopy which is going to be very useful tool to monitor trafficking of Francisella in the cells belonging to native immunity such as macrophages and dendritic cells. Methodology used for virus oriented projects involves real time PCR and real time RT‑PCR, microarrays and other up to date methodology.